• 제목/요약/키워드: Oncogenesis

검색결과 60건 처리시간 0.026초

Identification of Differentially Expressed Genes in Human Small Cell Lung Carcinoma Using Subtractive Hybridization

  • Ahn Seung-Ju;Choi Jae-Kyoung;Joo Young Mi;Lee Min-A;Choi Pyung-Rak;Lee Yeong-Mi;Kim Myong-Shin;Kim So-Young;Jeon Eun-Hee;Min Byung-In;Kim Chong-Rak
    • 대한의생명과학회지
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    • 제10권3호
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    • pp.195-202
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    • 2004
  • Lung cancer is a leading cause of cancer death worldwide; however, despite major advances in cancer treatment during the past two decades, the prognostic outcome of lung cancer patients has improved only minimally. This is largely due to the inadequacy of the traditional screening approach of diagnosis in lung cancer, which detects only well­established overt cancers and fails to identify precursor lesions in premalignant conditions of the bronchial tree. In recent years this situation has fundamentally changed with the identification of molecular abnormalities characteristic of premalignant changes; these concern tumour suppressor genes, loss of heterozygosity at crucial sites and activation of oncogenes. Basic knowledge at the molecular level has extremely important clinical implications with regard to early diagnosis, risk assessment and prevention, and therapeutic targets. In this study we used a 'cap-finder' subtractive hybridization method, 'long distance' polymerase chain reaction (PCR), streptavidin magnetic beads mediated subtraction, and spin column chromatography to detect differential expression genes of human small cell lung carcinoma. We have now isolated ninety two genes that expressed differentially in the human small cell lung carcinoma cells and analyzed of 12 clones with sequencing, nine cDNAs include tapasin (NGS-17) mRNA, BC200 alpha scRNA, chromosome 12q24 PAC RPCI3-462E2, protein phosphatase 1 (PPPICA), translocation protein 1 (TLOC1), ribosomal protein S24 (RPS24) mRNA, protein phosphatase (PPEF2), cathepsin Z, MDM2 gene and three novel genes. They may be oncogenesis­related proteins.

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The Fok1 Vitamin D Receptor Gene Polymorphism and 25(OH) D Serum Levels and Prostate Cancer among Jordanian Men

  • Atoum, Manar Fayiz;AlKateeb, Dena;Mahmoud, Sameer Ahmed AlHaj
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권6호
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    • pp.2227-2230
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    • 2015
  • Background: Prostate cancer (PCa) is one of the most commonly diagnosed neoplasms and the second leading cause of cancer death in men in the Western world. Vitamin D (1,25dihydroxy vitamin D) is linked to many biological processes that influence oncogenesis but data on relations between its genetic variants and cancer risk have been inconsistent. The aim of this study was to determine associations between a vitamin D genetic polymorphism and 25-hydroxyvitamin D [25(OH)D] levels and prostate cancer. Materials and Methods: Genomic DNA was extracted from 124 Jordanian prostate cancer patients and 100 healthy volunteers. Ethical approval was granted from the ethical committee at Hashemite University and written consent was given by all patients. PCR was used to amplify the vitamin D receptor Fok1 polymorphism fragment. 25(OH)D serum levels were measured by competitive immunoassay. Results: All genotypes were in Hardy-Weinberg equilibrium. Genotype frequency for Fok1 genotypes FF, Ff and ff was 30.7%, 61.3% and 8.06%, for prostate cancer patients, while frequencies for the control group was 28.0%, 66.0% and 6.0%, respectively, with no significant differences. Vitamin D serum level was significantly lower in prostate cancer patients (mean 7.7 ng/ml) compared to the control group (21.8 ng/ml). No significant association was noted between 25(OH)D and VDR Fok1 gene polymorphism among Jordanians overall, but significant associations were evident among prostate cancer patients (FF, Ff and ff : 25(OH)D levels of 6.2, 8.2 and 9.9) and controls (19.0, 22.5 and 26.3, respectively). An inverse association was noted between 25(OH)D serum level less than 10ng/ml and prostate cancer risk (OR 35.5 and 95% CI 14.3- 88.0). Conclusions: There is strong inverse association between 25(OH)D serum level less than 10ng/ml level and prostate cancer risk.

Associations between Single Nucleotide Polymorphisms of COX-2 and MMP-2 Genes and Colorectal Cancer Susceptibility in the Saudi Population

  • Shalaby, Manal Ali;Nounou, Howaida Attia;Alanazi, Mohammad Saud;Alharby, Othman;Azzam, Nahla;Saeed, Hesham Mahmoud
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권12호
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    • pp.4989-4994
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    • 2014
  • Background: It has been reported that COX-2 expression is associated with MMP-2 expression in thyroid and breast cancers, suggesting that MMPs are linked to COX-2-mediated carcinogenesis. Several polymorphisms within the MMP2 promoter region have been reported in cases with oncogenesis and tumor progression, especially in colorectal carcinogenesis. Materials and Methods: This research evaluated risk of association of the SNPs, including genes for COX-2 (AIG transition at +202) and MMP-2 (Crr transition at-1306), with colorectal cancer in 125 patients and 125 healthy controls. Results and Conclusions: Our data confirmed that MMP2 C-1306 T mutations were significantly more common in colon cancer patients than in our control Saudi population; p=O.0121. On the other hand in our study, there was no significant association between genotype distribution ofthe COX2 polymorphism and colorectal cancer; p=0.847. An elevated frequency ofthe mutated genotype in the control group as compared to the patients subjects indeed suggested that this polymorphism could decrease risk in the Saudi population. Our study confirmed that the polymorphisms that could affect the expressions of MMP-2 and COX-2 the colon cancer patients were significantly higher than that in the COX-2 negative group. The frequency of individuals with MMP2 polymorphisms in colon cancer patients was higher than individuals with combination of COX2 and MMP2 polymorphisms. Our study confirmed that individuals who carried the polymorphisms that could affect the expressions ofCOX2 are more susceptible to colon cancer. MMP2 regulatory polymorphisms could be considered as protective; further studies need to confirm the results with more samples and healthy subjects.

Upregulation and Clinicopathological Significance of Long Non-coding NEAT1 RNA in NSCLC Tissues

  • Pan, Lin-Jiang;Zhong, Teng-Fei;Tang, Rui-Xue;Li, Ping;Dang, Yi-Wu;Huang, Su-Ning;Chen, Gang
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권7호
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    • pp.2851-2855
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    • 2015
  • Background: Recent reports have shown that nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), contributes to the precise control of gene expression and is related to several human malignancies. However, limited data are available on the expression and function of NEAT1 in lung cancer. The major objective of the current study was to profile the expression and clinicopathological significance of NEAT1 in non-small cell lung cancers (NSCLCs). Materials and Methods: NEAT1 expression in 125 NSCLC cases and paired adjacent non-cancer tissues was assessed by real-time quantitative reverse transcription-PCR (qRT-PCR). Relationships between NEAT1 and clinicopathological factors were also investigated. Results: The relative level of NEAT1 was $6.98{\pm}3.74$ in NSCLC tissues, significantly elevated as compared to that of the adjacent non-cancer lung tissues ($4.83{\pm}2.98$, p<0.001). The area under curve (AUC) of high expression of NEAT1 to diagnose NSCLC was 0.684 (95% CI: 0.619~0.750, p<0.001). NEAT1 expression was positively correlated with patient age (r=-2.007, p=0.047), lymphatic metastasis (r=-2.731, p=0.007), vascular invasion (r=-3.617, p=0.001) and clinical TNM stage (r=-4.134, p<0.001). Conclusions: This study indicates that NEAT1 might be associated with oncogenesis and progression in NSCLC, and suggests application in molecular targeted therapy.

Tumor Infiltrating Lymphocytes in Ovarian Cancer

  • Gasparri, Maria Luisa;Attar, Rukset;Palaia, Innocenza;Perniola, Giorgia;Marchetti, Claudia;Donato, Violante Di;Farooqi, Ammad Ahmad;Papadia, Andrea;Panici, Pierluigi Benedetti
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권9호
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    • pp.3635-3638
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    • 2015
  • Several improvements in ovarian cancer treatment have been achieved in recent years, both in surgery and in combination chemotherapy with targeting. However, ovarian tumors remain the women's cancers with highest mortality rates. In this scenario, a pivotal role has been endorsed to the immunological environment and to the immunological mechanisms involved in ovarian cancer behavior. Recent evidence suggests a loss of the critical balance between immune-activating and immune-suppressing mechanisms when oncogenesis and cancer progression occur. Ovarian cancer generates a mechanism to escape the immune system by producing a highly suppressive environment. Immune-activated tumor infiltrating lymphocytes (TILs) in ovarian tumor tissue testify that the immune system is the trigger in this neoplasm. The TIL mileau has been demonstrated to be associated with better prognosis, more chemosensitivity, and more cases of optimal residual tumor achieved during primary cytoreduction. Nowadays, scientists are focusing attention on new immunologically effective tumor biomarkers in order to optimize selection of patients for recruitment in clinical trials and to identify relationships of these biomarkers with responses to immunotherapeutics. Assessing this point of view, TILs might be considered as a potent predictive immunotherapy biomarker.

Combined Effects Methylation of FHIT, RASSF1A and RARβ Genes on Non-Small Cell Lung Cancer in the Chinese Population

  • Li, Wen;Deng, Jing;Tang, Jian-Xin
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권13호
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    • pp.5233-5237
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    • 2014
  • Epigenetic modifications of tumour suppressor genes are involved in all kinds of human cancer. Aberrant promoter methylation is also considered to play an essential role in development of lung cancer, but the pathogenesis remains unclear.We collected the data of 112 subjects, including 56 diagnosed patients with lung cancer and 56 controls without cancer. Methylation of the FHIT, RASSF1A and RAR-${\beta}$ genes in DNA from all samples and the corresponding gene methylation status were assessed using the methylation-specific polymerase chain reaction (PCR, MSP). The results showed that the total frequency of separate gene methylation was significantly higher in lung cancer compared with controls (33.9-85.7 vs 0 %) (p<0.01).Similar outcomes were obtained from the aberrant methylation of combinations of any two or three genes (p<0.01). There was a tendency that the frequency of combinations of any two or three genes was higher in stage I+II than that in stage III+IV with lung cancer. However, no significant difference was found across various clinical stages and clinic pathological gradings of lung cancer (p>0.05).These observations suggest that there is a significant association of promoter methylation of individual genes with lung cancer risk, and that aberrant methylation of combination of any two or three genes may be associated with clinical stage in lung cancer patients and involved in the initiation of lung cancer tumorigenesis. Methylation of FHIT, RASSF1A and $RAR{\beta}$ genes may be related to progression of lung oncogenesis.

두경부 편평세포암종에서 p53, p21, EGFR 및 c-erbB-2 발현의 임상적 의의 (Clinical Significance of the Expression of p53, p21, EGFR and c-erbB-2 in Squamous Cell Carcinoma of the Head and Neck)

  • 이준한;도남용;박성용;김건형;조성일
    • 대한두경부종양학회지
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    • 제21권2호
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    • pp.139-145
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    • 2005
  • Background and Objectives: Because of squamous cell carcinoma of the head and neck undergoes a generally poor hospital course, the prognostic significance of the squamous cell carcinomas in head and neck have been evaluated to identify those features associated with aggressive biologic behavior according to the immunologic and histopathologic characteristics. Materials and Method: To assess the significance of EGFR, c-erbB-2, p21 and p53 protein in head and neck tumors and their correlation with prognostic factors, samples from 74 patients with squamous cell carcinomas of larynx, pharynx, and oral cavity were studied immunohistochemically. Results: EGFR, c-erbB-2, p21, and p53 protein were expressed 94.6%, 24.3%, 85.1%, and 55.4% in 74 cases of head and neck squamous cell carcinoma, respectively. The positive expression of EGFR was associated significantly with clinical stage and the negative expressions of p21 was associated significantly with histopathologic differentiation. There were no significant relationships between the reactivity of EGFR, c-erbB-2, p21, and p53 protein. Conclusion: The expression of EGFR, c-erbB-2, p21 and p53 protein could be related to oncogenesis, and the expression of p21 and EGFR protein can be used as a prognosticator in head and neck squamous cell carcinoma under certain limitations, but c-erbB-2 and p53 protein expression alone is not enough for evaluating prognosis of the carcinoma.

백혈병 세포주 HL-60에서 과루실 세포고사 유도 효과 (Apoptosis-inducing Effect of Fructus Trichosanthis in HL-60 Leukemic Cells)

  • 권강범;김은경;한미정;류도곤
    • 동의생리병리학회지
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    • 제19권4호
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    • pp.903-907
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    • 2005
  • Many naturally occurring plant extracts are studied for their beneficial effects for health and particularly on cancer. Apoptosis, or programmed cell death, occurs in both normal and pathological conditions, including cancer Dysregulation of apoptosis allows transformed cells to continually and uninhibitedly enter the cell cycle, thus perpetuating the sequence of mutation, genomic instability and, finally, oncogenesis. To investigate the apoptosis-inducing effect of the extract of Fructus Trichosanthis (EFT) on leukemic HL-60 cells and its mechanism, HL-60 cells in vitro in culture medium were given different doses of the extract. The inhibitory rate of cells were measured by microculture tetrazolium assay, cell apoptotic rate was detected by flow cytometry, morphology of cell apoptosis was observed by DAPI fluorescence staining, and the activations of caspases and PARP were detected using Western blotting analysis. The extract could activate the caspase-3 and caspase-8, induce PARP cleavage, inhibit growth of HL-60 cells, and cause apoptosis significantly The suppression was in dose-dependent manner. Marked morphological changes of cell apoptosis including condensation of chromatin and nuclear fragmentation were observed clearly by DAPI fluorescence staining especially. These results will provide strong laboratory evidence of EFT for clinical treatment of acute leukemia.

환경 및 생체시료 중 과불화 화합물의 분석 동향 (Analytical trend of perfluorinated compounds in environmental and biota samples)

  • 이원웅;장원희;표희수;강태석;홍종기
    • 분석과학
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    • 제23권4호
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    • pp.331-346
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    • 2010
  • 과불화 화합물(perfluorinated compounds, PFCs)은 열과 산성, 염기 등과 같은 화학적 조건에 높은 안정성을 갖고 있을 뿐만 아니라 발수성, 발유성, 방오성과 제품 친화적인 특징 때문에 다양한 산업소재로 활용되고 있으며, 근래에 이르러서는 대규모로 생산되고 있는 산업제품이다. 그러나 난분해성으로 인하여 환경 내에 잔류하여 전세계적으로 널리 분포하고 있을 뿐만 아니라 인체나 동식물에 이르는 생물체에 이르기까지 오염되어 분포하고 있다. 또한 인체를 비롯한 생물체에 장기적으로 축적될 시 암등을 유발할 가능성이 있다고 보고됨에 따라 이에 대한 관심이 증가하고 있다. 최근 스톡홀름 협약에서 과불화 화합물을 새로운 환경지속성오염물질(persistent organic pollutants, POPs)로 규정함에 따라 이에 대한 분석법의 중요성이 대두되고 있다. 본 연구에서는 다양한 환경 및 생체 시료 내에서 과불화 화합물의 분석법에 대한 연구의 중요성 및 문제점과 더불어 최근 연구 동향을 소개하였다.

두경부 편평세포암종의 발암 원인으로 인간유두종 바이러스(Human Papilloma Virus)의 역할 및 이와 관련된 발암 기전에 관한 연구 (The Etiologic Roles and Carcinogenic Mechanisms of Human Papilloma Virus in Head and Neck Squamous Cell Carcinoma)

  • 신동현;이세영;구본석;김세헌
    • 대한두경부종양학회지
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    • 제25권1호
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    • pp.28-32
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    • 2009
  • Background : The most frequently reported risk factors for head and neck suamous cell carcinoma are smoking and alcohol. But in a recent overview, human papilloma virus(HPV) infection was revealed the important carcinogenic factor in oropharyngeal cancer. We aimed to clarify whether HPV directly effects on the oncogenesis and biologic behavior of hean and neck squamous cell carcinoma by comparison with infection prevalence, and physical status of virus. Material and Method : We used HPV genotyping DNA chip(Biocore, Korea, Seoul) arrayed by multiple oligonucleotide probes of L1 sequence of 26 types of HPV and HPV genotypes are identified by fluorescence scanner. The copy numbers of HPV E2 and E6 open reading frames(ORF) were assessed using a TaqMan-based 5'-exonuclease quantitative real-time PCR assay. The ratio of E2 to E6 copy numbers was calculated to determine the physical status of HPV-16 viral gene. Results : We observed a significant difference in HPV prevalence between tonsillar cancer group and control group(73.1% vs. 11.6%), and most of the HPVs were type 16(87.2%) and integrated(94.1%) state. In terms of oral tongue cancer, we demonstrate that 30.5% has integrated HPV-16 in cancer tissue. But Glottic cancer only 1% is related to HPV-16 integration. Conclusion : This study revealed significant relationship of HPV prevalence with oropharyngeal and oral tongue squamous cell carcinoma. Most of HPV were 16 type and integrated or mixed, HPV-16 integration could be directly related to the carcinogenesis.